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CU-Boulder research highlights new DNA target area for cancer drugs

Tom Cech-led study pinpoints area of attack for yet-to-be-developed drugs

By Joe Rubino Camera Staff Writer

Posted:
10/28/2012 02:00:00 PM MDT

Tom Cech

Scientists at the University of Colorado's BioFrontiers Institute, in an article published in the journal Nature, have identified a new target area within human DNA that may be susceptible to future anti-cancer drugs.

The study, led by BioFrontiers Director Tom Cech and Chief Scientific Officer Leslie Leinwand, pinpoints a patch of amino acids at the ends of our chromosomes that, if blocked by a yet-to-be-developed drug, may prevent the reproduction of cancerous cells.

The patch is called the "TEL patch," according to the BioFrontiers Institute. Once the patch is modified, according to the study, the ends of the chromosome are made unable to recruit the telomerase enzyme, the activation of which scientists have linked to 90 percent of human cancers.

Cech, the 1989 Nobel Prize winner in chemistry and a Howard Hughes Medical Investigator, noted that a drug solution for cancer is still a long way off, but this development has highlighted a new, hopefully more effective, target area.

"The way we blocked telomerase action -- by changing single amino acids on the surface of the protein-- is good for 'proof of principle,' but of little practical use," Cech wrote in an e-mail last week. "The next step is to use this information in drug discovery. That is, find a small molecule drug that binds to the telomere protein at the site we've identified, which should then block telomerase action in the cancer cells."

Telomerase, the enzyme that keeps cells young and helps them live and multiply, has been a focus of cancer research for decades. It is known as the "immortality enzyme" because too much of it will make cells over-proliferate and become "immortal," leading to the growth of cancerous tumors, according to the Institute.

Cancer therapies have focused on limiting telomerase action to slow cancer growth, but the TEL patch study has identified a place that a drug could bind to chromosomes and block telomerase from attaching there.

Leinwand is biologist and a CU professor of molecular, cellular and developmental biology. Researchers in her lab worked closely with those in Cech's on the 3-year study.

"This work was really made possible by the fact that our labs are so close," Leinwand said in a news release. "My lab was able to provide the cell biology and understanding of genetics, and Tom's lab allowed us to explore the biochemistry. We have a unique situation at BioFrontiers, where labs and people comingle to make discoveries just like this."

Co-authors credited on the study include postdoctoral fellows Jayakrishnan Nandakumar and Ina Weidenfeld and former CU undergraduate student Caitlin Bell. Part of the BioFrontiers Institute's mission is to educate the new generation of interdisciplinary scientists, and Cech said Bell, who started as a volunteer in his lab as a freshman, was given lots of responsibility and worked with considerable independence on the study.

Bell, 23, earned her undergraduate degree in molecular, cellular and developmental biology in the spring, and is now in her first year of medical school at Vanderbilt University. She said she was paired with Nandakumar on the study, and performed many of the study's initial experiments, including cloning the different proteins that were used in testing.

She was part of the research team for the entire study and said it was hard to wait for the final product to at last be published -- but it was worth it.

"Obviously, the outcome could not have been any better," she said. "It has been awesome to finally see it written up and recognized."

Bell said she was very appreciative of the opportunity afforded her at the BioFrontiers Institute.

"I think just being able to work in Dr. Cech's lab, and be trained by such impressive scientists that are also great teachers, was the formative experience of my career at CU," she said.

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